Statin Nonusers Research Articles

Statins and SARS-CoV-2 Infection: Results of a Population-Based Prospective Cohort Study of 469749 Adults From 2 Canadian Provinces.

BackgroundSmall observational studies have suggested that statin users have a lower risk of dying with COVID‐19. We tested this hypothesis in a large, population‐based cohort of adults in 2 of Canada’s most populous provinces: Ontario and Alberta.Methods and ResultsWe examined reverse transcriptase–polymerase chain reaction swab positivity rates for SARS‐CoV‐2 in adults using statins compared with nonusers. In patients with SARS‐CoV‐2 infection, we compared 30‐day risk of all‐cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase–polymerase chain reaction swab for SARS‐CoV‐2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS‐CoV‐2 (3.6% versus 2.8%, P<0.001), but this difference was not significant after adjustment for baseline differences and propensity for statin use in each age stratum (adjusted odds ratio 1.00 [95% CI, 0.88–1.14], 1.00 [0.91–1.09], and 1.06 [0.82–1.38], respectively). In individuals younger than 75 years with SARS‐CoV‐2 infection, statin users were more likely to visit an emergency department, be hospitalized, be admitted to the intensive care unit, or to die of any cause within 30 days of their positive swab result than nonusers, but none of these associations were significant after multivariable adjustment. In individuals older than 75 years with SARS‐CoV‐2, statin users were more likely to visit an emergency department (28.2% versus 17.9%, adjusted odds ratio 1.41 [1.23–1.61]) or be hospitalized (32.7% versus 21.9%, adjusted odds ratio 1.19 [1.05–1.36]), but were less likely to die (26.9% versus 31.3%, adjusted odds ratio 0.76 [0.67–0.86]) of any cause within 30 days of their positive swab result than nonusers.ConclusionsCompared with statin nonusers, patients taking statins exhibit the same risk of testing positive for SARS‐CoV‐2 and those younger than 75 years exhibit similar outcomes within 30 days of a positive test. Patients older than 75 years with a positive SARS‐CoV‐2 test and who were taking statins had more emergency department visits and hospitalizations, but exhibited lower 30‐day all‐cause mortality risk.

Less statin associated adverse events after initiation of pitavastatin compared with atorvastatin and rosuvastatin

Abstract Background Statin associated adverse events (SAAEs), including hepatitis, myopathy and new onset diabetes mellitus (NODM), are major reasons that prevent the use of statins. We compared the risk of SAAEs among the commonly used statins to see if SAAEs were similar among the statins. Methods We retrieved data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2017, all statin-treated patients without diabetes at baseline were enrolled. We classified eligible patients into pitavastatin (2–4mg/day), moderate-intensity statin (MIS [atorvastatin 10–20 mg/day or rosuvastatin 5–10 mg/day]), and high-intensity statin group (HIS [atorvastatin ≥40 mg/day and rosuvastatin ≥20mg/day]). The study endpoint is a composite of safety events, including hepatitis, myopathy, and NODM. All patients were followed-up for at least one year until December 2018. We used propensity score to balance the baseline differences between the 3 statin groups (N=50935 in each group). Results After a mean follow up time of 3.08 years, the safety events occurred in 5014 patients in pitavastatin group (9.84%), 5542 in MIS group (10.88%), and 5343 in HIS group (10.49%). Multivariate Cox proportional hazards model showed that MIS and HIS statins were associated with a higher risk of safety events compared with pitavastatin (adjusted hazard ratio [aHR] 1.122, 95% confidence interval [CI] 1.08–1.17 for MIS and aHR 1.056, 95% CI 1.02–1.10 for HIS). Most events were NODM, with 4818 events in pitavastatin (9.46%), 5284 in MIS (10.37%), and 5113 in HIS group (10.04%). Multivariate Cox proportional hazard analysis showed higher risk of NODM in MIS (adjusted HR 1.111, 95% CI 1.07–1.16) and HIS (aHR 1.050, 95% CI 1.01–1.10) compared with pitavastatin. Time-varying HR analysis showed increased risk of NODM with use of all these statins for more than 1 year compared with non-statin users. Conclusions Pitavastatin was associated with a lower risk of SAAEs, especially NODM, compared with atorvastatin and rosuvastatin. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Orient EuroPharma Co., Ltd.

Effect of statin on progression of degenerative aortic root dilatation

Abstract Background Aortic root dilatation (ARD) is the most common thoracic aortic aneurysm (TAA). Causes of TAA include congenital and heritable disorders, degenerative disorders, inflammatory and infectious etiologies (1.) Hypertension management and smoking cessation are the two most important risk factor modification strategies to prevent rapid progression (&amp;gt;2 mm/year) of TAAs. Beta blockers and angiotensin receptor blockers are the preferred agents to treat HTN (5,6). Statin use is associated with a lower rate of progression of ascending arch and thoracoabdominal aortic aneurysms (2,3,4). However, their role in the progression of degenerative ARD remains unclear. Purpose To evaluate the association between statin use and progression of ARD. Methods A retrospective chart analysis was performed on 340 patients with a known diagnosis of degenerative ARD. Aortic root measurements were followed by serial transthoracic echocardiograms from the time of first diagnosis for a total of 10 years. The study population was dichotomized based on statin use. The mean change in ARD was calculated for each patient in millimeters. Baseline characteristics were compared between the groups. Multivariate adjusted linear regression models were used to estimate unit change in mean ARD change based on statin use. Results Patients in the statin group were older, more obese, with a higher prevalence of comorbidities and medication use compared to patients not on statin. Over a 10-year follow up, the mean increase in ARD was comparable for statin vs. non-statin users (0.83 mm vs. 0.73 mm, p=0.53). On a multivariate regression model adjusted for baseline demographics, risk factors and medication use, the statin group showed a 0.16 mm reduction in ARD compared to non-statin group but this decrease was not statistically significant (Table 1, p=0.47) Conclusion In patients with degenerative ARD on a pre-existing regimen of statin, there was no statistically significant change in ARD. Funding Acknowledgement Type of funding sources: None. Table 1

Statin use is associated with lower risk of new onset dementia in patients with heart failure

Abstract Background Increasing number of heart failure (HF) patients diagnosed with dementia due to improved treatment and aging population. Data relating to the association of statin use on the risk of dementia incidence among patients with HF are sparse. Methods Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (N=241,995) from 1996 to 2019. Propensity score matching was used to balance baseline covariates between statin nonusers (167,738 patients) with statin users (74,257 patients). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of incident dementia associated with statin use. Results Of all eligible subjects, the mean age was 76.5±13.0 years, 115,371 (47.7%) was male. Over a median follow-up of 2.7 years (interquartile range [IQR]: 0.6 to 6.7), 13,482 (5.6%) patients were diagnosed with dementia including Alzheimer's disease (N=5,253), senile dementia uncomplicated (N=4,273), arteriosclerotic dementia (N=3,262), and others (N=694). Statin use (vs. none) was associated with a 58% lower risk of dementia incidence (multivariable-adjusted sub-distribution hazard ratio [SHR]=0.42; 95% Confidence Interval [CI], 0.38 to 0.46) after accounting for death as a competing risk. Moreover, the male gender was associated with a 51% lower risk of dementia incidence (multivariable-adjusted SHR=0.59; 95% CI (0.54–0.65) compared with females. Conclusion Our study suggests that there is substantial sex difference in the incidence of dementia among HF patients. Moreover, statin use is associated with a significantly lower risk of incident dementia in HF. Funding Acknowledgement Type of funding sources: None.

Statins for primary prevention among elderly men and women

Abstract Background The debate about statins in primary prevention of cardiovascular (CV) disease is still alive, especially in old and very old adults. Purpose We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. Methods We included in our analysis 5,619 people aged 65 years or older from the ISACS (International Survey of Acute Coronary Syndrome) Archives (NCT04008173) who presented to hospital with a first manifestation of CV disease. Participants were stratified as statin users versus nonusers and as old (65 to 75 years) versus very old (76 years or over) adults. We estimated the effects of statins on the most severe clinical manifestation of CV disease, namely ST segment elevation myocardial infarction (STEMI), using inverse probability of treatment weighting models. Estimates were compared by test of interaction on the log scale. Results The risk of STEMI was much lower in statin users than in nonusers in both patients aged 65 to 75 years (14.7% absolute risk reduction; relative risk [RR] ratio: 0.55, 95% CI 0.45 to 0.66) and those aged 76 years and older (13.3% absolute risk reduction; RR ratio: 0.58, 95% CI 0.46 to 0.72). Estimates were similar in patients with and without history of hypercholesterolemia (interaction test; p value= 0.2408). Proportional reductions in STEMI diminished with female sex in the old (p for interaction=0.002), but not in the very old age (p for interaction=0.26). We also observed a remarkable reduction in the risk of 30- day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR ratio: 0.39; 95% CI 0.23 – 0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR ratio 0.37; 95% CI 0.17 – 0.82 for patients aged 65 to 75 years old; interaction test, p value=0.4570). Conclusion Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Funding Acknowledgement Type of funding sources: None.

Statin Use and COVID-19 Infectivity and Severity in South Korea: Two Population-Based Nationwide Cohort Studies.

BackgroundBasic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking.ObjectiveWe investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive ventilation, or death) between statin users and nonusers.MethodsTwo independent population-based cohorts were analyzed, and we investigated the differences in SARS-CoV-2 test positivity and severe clinical outcomes of COVID-19, such as admission to the intensive care unit, invasive ventilation, or death, between statin users and nonusers. One group comprised an unmatched cohort of 214,207 patients who underwent SARS-CoV-2 testing from the Global Research Collaboration Project (GRCP)-COVID cohort, and the other group comprised an unmatched cohort of 74,866 patients who underwent SARS-CoV-2 testing from the National Health Insurance Service (NHIS)-COVID cohort.ResultsThe GRCP-COVID cohort with propensity score matching had 29,701 statin users and 29,701 matched nonusers. The SARS-CoV-2 test positivity rate was not associated with statin use (statin users, 2.82% [837/29,701]; nonusers, 2.65% [787/29,701]; adjusted relative risk [aRR] 0.97; 95% CI 0.88-1.07). Among patients with confirmed COVID-19 in the GRCP-COVID cohort, 804 were statin users and 1573 were matched nonusers. Statin users were associated with a decreased likelihood of severe clinical outcomes (statin users, 3.98% [32/804]; nonusers, 5.40% [85/1573]; aRR 0.62; 95% CI 0.41-0.91) and length of hospital stay (statin users, 23.8 days; nonusers, 26.3 days; adjusted mean difference –2.87; 95% CI –5.68 to –0.93) than nonusers. The results of the NHIS-COVID cohort were similar to the primary results of the GRCP-COVID cohort.ConclusionsOur findings indicate that prior statin use is related to a decreased risk of worsening clinical outcomes of COVID-19 and length of hospital stay but not to that of SARS-CoV-2 infection.

Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas.

OBJECTIVESulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction.RESEARCH DESIGN AND METHODSAs an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions.RESULTSAfter establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor.CONCLUSIONSWe have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.

Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort

ObjectiveTo determine the effect of statins on risk of cancer in patients with interstitial lung disease (ILD) and pulmonary fibrosis.SettingWe retrospectively enrolled patients with ILD and pulmonary fibrosis and divided...

Mortality associated with stopping statins in the oldest-old - with and without ischemic heart disease.

The association between stopping statins and 1-year mortality in the general population of the oldest-old – with or without ischemic heart disease (IHD) – has been studied herein for the first time.This was a retrospective study. Included were all consecutive patients (n = 369) aged 80 years or more (mean age 87.8 years) hospitalized in a single Geriatrics department during 1 year. The study group included 140 patients in whom statins were stopped upon admission (statin stoppers). The control group included 229 patients who did not use statins in the first place (statin non-users). All-cause 1-year mortality rates were studied in both groups following propensity score matching and in IHD patients separately.Overall, 110 (29.8%) patients died during the year following admission: 38 (27.1%) statin stoppers and 72 (31.4%) statin non-users (P = .498). Cox regression analysis showed no association between stopping statins and 1-year mortality in the crude analysis (hazard ratio [HR] 0.976, 95% confidence interval [CI] 0.651–1.463, P = .907) and following propensity score matching (HR 1.067, 95%CI 0.674–1.689, P = .782). Among 108 IHD patients, 38 (35.2%) patients died during the year following admission: 18 (27.7%) statin stoppers and 20 (46.5%) statin non-users (P = .059). Cox regression analysis showed a nearly significant association between stopping statins (rather than not using statins) in IHD patients and lower 1-year mortality (HR 0.524, 95%CI 0.259–1.060, P = .072).Hence, stopping statins in the general population of the oldest-old – with or without IHD – is possibly safe. Future studies including the oldest-old statin continuers are warranted to confirm this observation.

Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19.

PurposeCOVID-19 is characterized by dysfunctional immune responses and metabolic derangements, which in some, lead to multi-organ failure and death. Statins are foundational lipid-lowering therapeutics for cardiovascular disease and also possess beneficial immune-modulating properties. Because of these immune-modulating properties, some have suggested their use in COVID-19. We sought to investigate the association between statin use and mortality in patients hospitalized with COVID-19.MethodsFive thousand three hundred seventy-five COVID-19 patients admitted to Mount Sinai Health System hospitals in New York between February 27, 2020, and December 3, 2020, were included in this analysis. Statin use was classified as either non-user, low-to-moderate-intensity user, or high-intensity user. Multivariate Cox proportional hazards models were used to evaluate in-hospital mortality rate. Considered covariates were age, sex, race, and comorbidities.ResultsCompared to non-statin users, both low-to-moderate-intensity (adjusted hazard ratio; aHR 0.62, 95% confidential intervals; CI 0.51–0.76) and high-intensity statin users (aHR 0.53, 95% CI 0.43–0.65) had a reduced risk of death. Subgroup analysis of 723 coronary artery disease patients showed decreased mortality among high-intensity statin users compared to non-users (aHR 0.51, 95% CI 0.36–0.71).ConclusionsStatin use in patients hospitalized with COVID-19 was associated with a reduced in-hospital mortality. The protective effect of statin was greater in those with coronary artery disease. These data support continued use of statin therapy in hospitalized patients with COVID-19. Clinical trials are needed to prospectively determine if statin use is effective in lowering the mortality in COVID-19 and other viral infections.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10557-021-07263-2.

Statin use for primary prevention in patients with type 2 diabetes: Can it benefit all ages? – A nationwide propensity-matched cohort study

AimsThis study aims to investigate whether statin use is associated with a reduction in CVD and mortality in patients with type 2 diabetes without pre-existing CVD. MethodsA propensity score-matched cohort analysis using retrospective data was created. Statin users received at least a 90-day prescription, and never used statin before initiation of the study. Statin non-users never received statin throughout the study. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death, and secondary outcome was an individual event. ResultsThe propensity score matched cohort included 168,045 statin users and 168,045 non-users (mean age 57 years; median follow-up 5.0 years). Compared to statin non-users, the hazard ratio (HR) was 0.72 (95% confidence interval [CI] 0.70–0.73; P < 0.001) for composite outcomes, 0.80 (0.76–0.84; P < 0.001) for MI, 0.74 (0.71–0.76; P < 0.001) for stroke, and 0.68 (0.66–0.70; P < 0.001) for all-cause death in statin users. The risk reduction was most prominent in subjects aged 40–74 years, attenuated but significant in those aged ≥75 years, and not significant in those aged <40 years. ConclusionsStatin showed a protective effect against CVD and all-cause death in type 2 diabetes; this effect was reduced beyond the age of 75 years and disappeared in young patients aged <40 years.

Anticancer Effect of Statins in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma.

The anticancer effect of statins is drawing attention. However, it is unclear whether statin use reduces the risk of hepatocellular carcinoma (HCC) recurrence in patients who undergo liver transplantation (LT) for HCC. Consecutive patients who underwent LT for HCC between 1995 and 2019 were enrolled. The effects of statins on HCC recurrence and mortality were compared between statin user and statin nonuser groups. We performed the analyses in a variety of ways, including inverse probability treatment weighting (IPTW) methods to balance any confounders and the landmark method to avoid immortal time bias. A total of 430 patients were enrolled, among whom 323 (75.1%) were statin nonusers and 107 (24.9%) were statin users. During a median of 64.9months (IQR, 26.1-122.6 months) of follow-up, 79 patients (18.4%) had HCC recurrence and 111 (25.8%) died. Among those who died, 53 (47.7%) were identified as HCC-related mortalities. Statin use was a predictor of HCC recurrence (adjusted hazard ratio [HR],0.3; 95% confidence interval [CI], 0.1-0.6; P=0.002), all-cause mortality (adjusted HR,0.3; 95% CI, 0.2-0.5; P<0.001), and HCC-related mortality (adjusted HR,0.4; 95% CI, 0.2-0.9; P=0.03). The effects of statin use on clinical outcomes were also identified through IPTW analysis. There was a dose-dependent relationship between statin use and HCC recurrence. The anticancer effect of statins on HCC recurrence was consistently significant across multivariable-stratified and sensitivity analyses. Statin use significantly reduced the risk of HCC recurrence and improved the survival of patients who underwent LT for HCC.

Statins in mature B-cell lymphomas and leukaemias.

Statins in mature B-cell lymphomas and leukaemias.

Efficacy of Statin Treatment According to Baseline Renal Function in Korean Patients with Acute Myocardial Infarction Not Requiring Dialysis Undergoing Newer-Generation Drug-Eluting Stent Implantation.

We investigated the 2-year efficacy of statin treatment according to baseline renal function in patients with acute myocardial infarction (AMI) not requiring dialysis undergoing newer-generation drug-eluting stent (DES) implantation. A total of 18,875 AMI patients were classified into group A (statin users, n = 16,055) and group B (statin nonusers, n = 2820). According to the baseline estimated glomerular filtration rate (eGFR; ≥90, 60–89, 30–59 and <30 mL/min/1.73 m2), these two groups were sub-classified into groups A1, A2, A3 and A4 and groups B1, B2, B3 and B4. The major adverse cardiac events (MACE), defined as all-cause death, recurrent MI (re-MI) and any repeat revascularization, were evaluated. The MACE (group A1 vs. B1, p = 0.002; group A2 vs. B2, p = 0.007; group A3 vs. B3, p < 0.001; group A4 vs. B4, p < 0.001), all-cause death (p = 0.006, p < 0.001, p < 0.001, p < 0.001, respectively) and cardiac death (p = 0.004, p < 0.001, p < 0.001, p < 0.001, respectively) rates were significantly higher in statin nonusers than those in statin users. Despite the beneficial effects of statin treatment, the MACE (group A1 vs. A2 vs. A3 vs. A4: 5.2%, 6.4%, 10.1% and 18.5%, respectively), all-cause mortality (0.9%, 1.8%, 4.6% and 12.9%, respectively) and cardiac death (0.4%, 1.0%, 2.6% and 6.8%, respectively) rates were significantly increased as eGFR decreased in group A. These results may be related to the peculiar characteristics of chronic kidney disease, including increased vascular calcification and traditional or nontraditional cardiovascular risk factors. In the era of newer-generation DESs, although statin treatment was effective in reducing mortality, this beneficial effect was diminished in accordance with the deterioration of baseline renal function.

The Association Between the Use of Statins and Clinical Outcomes in Patients with COVID-19: A Systematic Review and Meta-analysis.

PurposePreviously, we have reported potential clinical benefits with the use of statins in patients with coronavirus disease 2019 (COVID-19) in a meta-analysis, where there was a significantly reduced hazard for a fatal or severe course of illness with the use of statins, but the meta-analysis was limited by the small number of studies included, with small heterogeneity among studies, due to the unavailability of more studies at the point of literature search. We aimed to perform an updated systematic review and meta-analysis to summarize the existing evidence on the effect of statins on the clinical outcomes of patients with COVID-19.MethodsElectronic databases, including PubMed, Google Scholar, and Scopus, and preprint servers were searched (last updated June 3, 2021) to identify studies investigating the association between the use of statins in patients with COVID-19 and the development of severe disease and/or mortality. Random-effects model meta-analyses were performed to estimate the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CIs). The outcomes of interest were (1) all-cause mortality and (2) a composite endpoint of severe illness of COVID-19.ResultsUpon systematic literature search, we identified 35 studies, of which 32 studies reported the outcome of all-cause mortality and 15 studies reported the composite endpoint of severe COVID-19 illness between statin users versus non-statin users with COVID-19. Our meta-analysis revealed that the use of statins was associated with a significantly lower risks of all-cause mortality (HR = 0.70, 95% CI 0.58–0.84, n = 21,127, and OR = 0.63, 95% CI 0.51–0.79, n = 115,097) and the composite endpoint of severe illness (OR = 0.80, 95% CI 0.73–0.88, n = 10,081) in patients with COVID-19, compared to non-use of statins, at the current sample size.ConclusionStatin use is associated with a better prognosis in patients with COVID-19. Our findings provide a rationale to investigate the use of statins among patients with COVID-19 in large scale clinical trials.

Statin Therapy in Patients Undergoing Thoracic Aorta Replacement for Aortic Aneurysms.

Background Patients undergoing surgery for thoracic aortic aneurysms receive statin therapy out of proportion to cardiovascular comorbidity. We sought to determine the prevalence of statin use among patients presenting for thoracic aortic aneurysm surgery and investigate its effect on outcomes. Methods From January 1, 2005 to January 1, 2011, 1,839 consecutive patients underwent aortic replacement for degenerative thoracic aortic aneurysm at Cleveland Clinic. Of these, 771 (42%) were on statins preoperatively. Statin users (vs. nonstatin users) were older (65 ± 11 vs. 56 ± 16 years) and had more hypertension (78 vs. 59%). Propensity matching based on 56 preoperative variables other than lipid levels was used to compare outcomes among 570 matched patient pairs (74% of possible pairs). Results Propensity-matched statin and nonstatin users were aged 64 ± 11 years, 394 (69%) versus 387 (68%) were male, and 437 (77%) versus 442 (78%) had ascending aortic aneurysms, respectively. Overall, 25% of patients were followed for more than 8.2 years and 10% for more than 10 years. Perioperative outcomes were similar, including hospital mortality (11 [1.9%] vs. 5 [0.88%]) and stroke (22 [3.9%] vs. 13 [2.3%]), but 16 statin users (2.8%) versus 5 nonstatin users (0.88%) required temporary dialysis after surgery ( p = 0.02). At 6 years, 3.7% of statin users versus 5.1% of nonstatin users ( p [log-rank] = 0.5) underwent further aortic surgery, and at 10 years, mortality was 25% in both groups ( p > 0.5). Conclusion Patients presenting for thoracic aortic aneurysm surgery frequently receive unnecessary statins. Additionally, statin use was associated with more postoperative renal failure, but not less intermediate-term risk for aortic reintervention or all-cause mortality after surgery. Therefore, presence of a thoracic aortic aneurysm should not be considered an indication for statin therapy in the absence of well-established indications.

Medication use and mammographic breast density.

A dense breast on mammogram is a strong risk factor for breast cancer. Identifying factors that reduce mammographic breast density could thus provide insight into breast cancer prevention. Due to the limited number of studies and conflicting findings, we investigated the associations of medication use (specifically statins, aspirin, and ibuprofen) with mammographic breast density. We evaluated these associations in 775 women who were recruited during an annual screening mammogram at Washington University School of Medicine, St. Louis. We measured mammographic breast density using Volpara. We used multivariable-adjusted linear regressions to determine the associations of medication use (statins, aspirin, and ibuprofen) with mammographic breast density. Least squared means were generated and back-transformed for easier interpretation. The mean age of study participants was 52.9years. Statin use in the prior 12months was not associated with volumetric percent density or dense volume, but was positively associated with non-dense volume. The mean volumetric percent density was 8.6% among statin non-users, 7.2% among women who used statins 1-3days/week, and 7.3% among women who used statins ≥ 4days/week (p trend = 0.07). The non-dense volume was 1297.1cm3 among statin non-users, 1368.7cm3 among women who used statins 1-3days/week, and 1408.4cm3 among those who used statins ≥ 4days/week (p trend = 0.02). We did not observe statistically significant differences in mammographic breast density by aspirin or ibuprofen use. Statin, aspirin, and ibuprofen use was not associated with volumetric percent density and dense volume, but statin use was positively associated with non-dense volume. Any potential associations of these medications with breast cancer risk are unlikely to be mediated through an effect on volumetric percent density.

Hyperlipidemia and Statin Use on the Progression of Osteoarthritis: A Systematic Review.

Osteoarthritis (OA) is progressive wear and tear disease that affects multiple joints, including knees, hips, and spine. OA causes structural damage to joints. Although hypertension, type II diabetes, and hyperlipidemia have a silent effect, for the most part, the addition of osteoarthritis has a limiting and debilitating impact on patients. Common symptoms of OA include joint pain, joint swelling, limitations in range of motion that is impacting one’s quality of life. The question being investigated in this systematic review is whether hyperlipidemia or the use of statin has any effect on osteoarthritis and progression of osteoarthritis. This systematic review of 13 articles was done to explore if there is an effect of hyperlipidemia and statin use on the progression of osteoarthritis. This study included 6,974,538 total participants. Eight studies out of the 13 investigated the effect of statin use. Out of the 13 articles, five studies investigated the impact of lipid levels on OA. The total participants cannot be divided into statin users and non-users because some studies did not divide the participants into two groups. Studies that investigated the effect of lipid levels on OA were studied based on age. Some included only women in their study, and one study was solely conducted in the military population. Therefore, these studies cannot be divided based on age. Further research is needed to significantly conclude either the positive or negative correlation of hyperlipidemia and statin use on osteoarthritis and its progression.

Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis

Background and aimsStatin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality. MethodsA systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus non-users. Results22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 ± 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58–100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Meta-analysis of 12 studies (n = 72,881, weighted age 65 ± 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities. ConclusionsThis meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients.

Statin Use Is Associated with Decreased Mortality in Multiple Myeloma— a SEER Medicare Study

IntroductionStatins are a groups of drugs used in the treatment of hyperlidemia and in primary and secondary prevention of cardiovascular disease. Recently, there has been increasing interest in statins for their ability to improve survival and reduce risk of cancer due to their pleiotropic effects. Observational studies have reported survival benefit among patients with several cancers including pancreatic cancer, ovarian cancer and colorectal cancer. It has also been shown to reduce incidence risk in hematologic malignancies including lymphoid neoplasms. Recently, Sanfillipo et al (J Clin Oncol 2016 34:4008-4014) reported that statin use among patients with Multiple Myeloma (MM) was associated with decreased mortality in a Veteran Affairs (VA) database. We attempted to replicate these findings among older patients with MM using data from SEER-Medicare database.MethodsAll cases of MM diagnosed 2008-2013 in the SEER-Medicare claims were extracted along with their associated Medicare claims data from 2007-2014. Incomplete cases including: those diagnosed prior to age 65, death certificate or autopsy cases, and those not enrolled in Medicare Part A (inpatient), B (outpatient), and D (prescription) were excluded. Cases of suspected smoldering MM, those without MM defining “CRAB” symptoms and not treated within 6 months following diagnosis, were excluded using a pre-established algorithm (Fakhri, et al,Blood 2016 128:2348). Statin users, defined as having 2 or more prescriptions for statins within 1 year before and after diagnosis of MM, were identified by Part D claims. ICD-9 codes were used to identify patients with chronic kidney disease (CKD). Charlson comorbidity index (CCI) was calculated using a previously established algorithm. Receipt of novel MM agents as first-line therapy and stem cell transplant and bisphosphonate utilization within 1 year following diagnosis were defined as the presence or absence of the corresponding ICD-9 and HCPCS codes. Baseline characteristics were compared between statin users and non-users by Chi-square test and Student's T-test as appropriate. Multivariate analysis was performed by Cox proportional hazard modeling method. Statin exposure was also assessed as a time-dependent covariate to account for immortal time bias. All statistical analysis was performed using SAS software 9.4 (Cary, NC, USA)Results5935 patients were included in the study of which 1779 were statin users. Descriptive data is shown in table 1. Statin users tended to be slightly older, had a higher rate of CKD and higher mean CCI, but were slightly more likely to undergo ASCT (Autologous stem cell transplant). In the survival analysis, statin use (time-dependent) was associated with decreased mortality with an adjusted hazard ratio of (aHR- 0.91, 0.85-0.98, p=0.008). Use of novel agents, bisphosphonates, and stem cell transplant were all associated with decreased mortality; increasing age and CCI were associated with increased mortality. The full multivariate results are shown in table 2.ConclusionsStatins as a class of drugs exert their effect on mevalonate pathway by inhibiting HMG-CoA reductase for their cholesterol lowering effect and this disruption of mevalonate pathway has also been shown to induce apoptosis in MM cells. In vitro studies of MM cells have also shown to induce cell death and decrease proliferation when exposed to statins. This susceptibility of MM cells to statins in laboratory experiments has been further supported by findings in retrospective studies with Epstein et al (Int. J. Cancer 2017 141: 480-487) reporting reduced incidence of MM with statin use and Sanfillipo et al showing decreased mortality with statin use among patients with MM.In the present study we found that statin use decreased mortality by 9%. Our results are similar to the findings reported by Sanfillipo et al and further support a potential benefit of statin use among patients with MM. These results should be evaluated further in prospective clinical trials. [Display omitted] DisclosuresVij:Celgene: Honoraria; Konypharma: Honoraria; Takeda: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Meyers-Squibb: Honoraria; Jazz: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Research Funding. Wildes:Carevive Systems Inc: Consultancy; Janssen: Consultancy.